Development of the ACTIVE framework to describe stakeholder involvement in systematic reviews

Objectives Involvement of patients, health professionals, and the wider public (‘stakeholders’) is seen to be beneficial to the quality, relevance and impact of research and may enhance the usefulness and uptake of systematic reviews. However, there is a lack of evidence and resources to guide researchers in how to actively involve stakeholders in systematic reviews. In this paper we report the development of the ACTIVE framework to describe how stakeholders are involved in systematic reviews. Methods We developed a framework using methods previously described in the development of conceptual frameworks relating to other areas of public involvement, including: literature searching, data extraction, analysis, and categorisation. A draft ACTIVE framework was developed and then refined after presentation at a conference workshop, before being applied to a series of example systematic reviews. Data extracted from 32 systematic reviews, identified in a systematic scoping review, were categorised against pre-defined constructs, including: who was involved, how stakeholder were recruited, the mode of involvement, at what stage there was involvement and the level of control or influence. Results The final ACTIVE framework described whether patients, carers and/or families, and/or other stakeholders (including health professionals, health decision makers and funders) were involved. We defined: recruitment as either open or closed; the approach to involvement as either onetime, continuous or combined; and the method of involvement as either direct or indirect. The stage of involvement in reviews was defined using the Cochrane Ecosystem stages of a review. The level of control or influence was defined according to the roles and activities of stakeholders in the review process, and described as the ACTIVE continuum of involvement. Conclusions The ACTIVE framework provides a structure with which to describe key components of stakeholder involvement within a systematic review, and we have used this to summarise how stakeholders have been involved in a subset of varied systematic reviews. The ACTIVE continuum of involvement provides a new model that uses tasks and roles to detail the level of stakeholder involvement. This work has contributed to the development of learning resources aimed at supporting systematic review authors and editors to involve stakeholders in their systematic reviews. This framework may support the decision-making of systematic review authors in planning how to involve stakeholders in future review

A novel grass hybrid to reduce flood generation in temperate regions

We report on the evaluation of a novel grass hybrid that provides efficient forage production and could help mitigate flooding. Perennial ryegrass (Lolium perenne) is the grass species of choice for most farmers, but lacks resilience against extremes of climate. We hybridised L. perenne onto a closely related and more stress-resistant grass species, meadow fescue Festuca pratensis. We demonstrate that the L. perenne × F. pratensis cultivar can reduce runoff during the events by 51% compared to a leading UK nationally recommended L. perenne cultivar and by 43% compared to F. pratensis over a two year field experiment. We present evidence that the reduced runoff from this Festulolium cultivar was due to intense initial root growth followed by rapid senescence, especially at depth. Hybrid grasses of this type show potential for reducing the likelihood of flooding, whilst providing food production under conditions of changing climate

Deep roots and soil structure

In this opinion article we examine the relationship between penetrometer resistance and soil depth in the field. Assuming that root growth is inhibited at penetrometer resistances > 2.5 MPa, we conclude that in most circumstances the increases in penetrometer resistance with depth are sufficiently great to confine most deep roots to elongating in existing structural pores. We suggest that deep rooting is more likely related to the interaction between root architecture and soil structure than it is to the ability of a root to deform strong soil. Although the ability of roots to deform strong soil is an important trait, we propose it is more closely related to root exploration of surface layers than deep rooting

Evolution of Blind Beetles in Isolated Aquifers: A Test of Alternative Modes of Speciation

Evidence is growing that not only allopatric but also sympatric speciation can be important in the evolution of species. Sympatric speciation has most convincingly been demonstrated in laboratory experiments with bacteria, but field-based evidence is limited to a few cases. The recently discovered plethora of subterranean diving beetle species in isolated aquifers in the arid interior of Australia offers a unique opportunity to evaluate alternative modes of speciation. This naturally replicated evolutionary experiment started 10-5 million years ago, when climate change forced the surface species to occupy geographically isolated subterranean aquifers. Using phylogenetic analysis, we determine the frequency of aquifers containing closely related sister species. By comparing observed frequencies with predictions from different statistical models, we show that it is very unlikely that the high number of sympatrically occurring sister species can be explained by a combination of allopatric evolution and repeated colonisations alone. Thus, diversification has occurred within the aquifers and likely involved sympatric, parapatric and/or microallopatric speciation

High Genetic Diversity and Fine-Scale Spatial Structure in the Marine Flagellate Oxyrrhis marina (Dinophyceae) Uncovered by Microsatellite Loci

Free-living marine protists are often assumed to be broadly distributed and genetically homogeneous on large spatial scales. However, an increasing application of highly polymorphic genetic markers (e.g., microsatellites) has provided evidence for high genetic diversity and population structuring on small spatial scales in many free-living protists. Here we characterise a panel of new microsatellite markers for the common marine flagellate Oxyrrhis marina. Nine microsatellite loci were used to assess genotypic diversity at two spatial scales by genotyping 200 isolates of O. marina from 6 broad geographic regions around Great Britain and Ireland; in one region, a single 2 km shore line was sampled intensively to assess fine-scale genetic diversity. Microsatellite loci resolved between 1–6 and 7–23 distinct alleles per region in the least and most variable loci respectively, with corresponding variation in expected heterozygosities (He) of 0.00–0.30 and 0.81–0.93. Across the dataset, genotypic diversity was high with 183 genotypes detected from 200 isolates. Bayesian analysis of population structure supported two model populations. One population was distributed across all sampled regions; the other was confined to the intensively sampled shore, and thus two distinct populations co-occurred at this site. Whilst model-based analysis inferred a single UK-wide population, pairwise regional FST values indicated weak to moderate population sub-division (0.01–0.12), but no clear correlation between spatial and genetic distance was evident. Data presented in this study highlight extensive genetic diversity for O. marina; however, it remains a substantial challenge to uncover the mechanisms that drive genetic diversity in free-living microorganisms

An integrated genomic analysis of anaplastic meningioma identifies prognostic molecular signatures.

Anaplastic meningioma is a rare and aggressive brain tumor characterised by intractable recurrences and dismal outcomes. Here, we present an integrated analysis of the whole genome, transcriptome and methylation profiles of primary and recurrent anaplastic meningioma. A key finding was the delineation of distinct molecular subgroups that were associated with diametrically opposed survival outcomes. Relative to lower grade meningiomas, anaplastic tumors harbored frequent driver mutations in SWI/SNF complex genes, which were confined to the poor prognosis subgroup. Aggressive disease was further characterised by transcriptional evidence of increased PRC2 activity, stemness and epithelial-to-mesenchymal transition. Our analyses discern biologically distinct variants of anaplastic meningioma with prognostic and therapeutic significance

STROBE-X: A probe-class mission for x-ray spectroscopy and timing on timescales from microseconds to years

We describe the Spectroscopic Time-Resolving Observatory for Broadband Energy X-rays (STROBE-X), a probeclass mission concept that will provide an unprecedented view of the X-ray sky, performing timing and spectroscopy over both a broad energy band (0.2-30 keV) and a wide range of timescales from microseconds to years. STROBE-X comprises two narrow-field instruments and a wide field monitor. The soft or low-energy band (0.2-12 keV) is covered by an array of lightweight optics (3-m focal length) that concentrate incident photons onto small solid-state detectors with CCD-level (85-175 eV) energy resolution, 100 ns time resolution, and low background rates. This technology has been fully developed for NICER and will be scaled up to take advantage of the longer focal length of STROBE-X. The higher-energy band (2-30 keV) is covered by large-area, collimated silicon drift detectors that were developed for the European LOFT mission concept. Each instrument will provide an order of magnitude improvement in effective area over its predecessor (NICER in the soft band and RXTE in the hard band). Finally, STROBE-X offers a sensitive wide-field monitor (WFM), both to act as a trigger for pointed observations of X-ray transients and also to provide high duty-cycle, high time-resolution, and high spectral-resolution monitoring of the variable X-ray sky. The WFM will boast approximately 20 times the sensitivity of the RXTE All-Sky Monitor, enabling multi-wavelength and multi-messenger investigations with a large instantaneous field of view. This mission concept will be presented to the 2020 Decadal Survey for consideration

Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+\u2009ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+\u2009ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA